4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivative as antibacterial agents

Abstract

Novel naphthyridine-, quinoline- and benzoxazinecarboxylic acids as antibacterial agents are described as well as methods for their manufacture, formulation, and use in treating bacterial infections including the description of certain novel intermediates used in the manufacture of the antibacterial agents.

We claim: 
     
       1. A compound of the formula ##STR22## wherein Z is ##STR23## Y is NH 2 , NHR, NRR', OR, or OH wherein R and R', are each independently an alkyl of from one to six carbon atoms or a cycloalkyl of from three to six carbon atoms,; X is CH, CF, CCl, CBr, COR, COH,; n is 1, 2, 3, or 4; n' is 1, 2, 3, or 4 wherein n+n, is a total of 2, 3, 4, or 5, and n," is 0, 1, or 2; R 1  is hydrogen, alkyl having from one to six carbon atoms or a cation; R 2  is alkyl having from one to four carbon atoms, vinyl, haloalkyl, or hydroxyalkyl having from two to four carbon atoms, or cycloalkyl having three to six carbon atoms; R 3  is hydrogen, alkyl having from one to four carbon atoms or cycloalkyl having three to six carbon atoms; R 4  is hydrogen, alkyl from one to four carbon atoms, hydroxyalkyl having two to four carbon atoms, trifluoroethyl or R 7  CO-- wherein R 7  is alkyl having from one to four carbon atoms, or alkoxy having from one to four carbon atoms; R 5  is hydrogen, or alkyl having from one to three carbon atoms; R 6  is hydrogen or alkyl having from one to three carbon atoms; and the pharmaceutically acceptable acid addition or base salts thereof. 
     
     
       2. A compound as claimed in claim 1, wherein R 2  is ethyl, vinyl, 2-fluoroethyl or cyclopropyl. 
     
     
       3. A compound as claimed in claim 2, wherein X is CF, CCl, or CBr. 
     
     
       4. A compound as claimed in claim 2, wherein R 1  is hydrogen or a pharmaceutically acceptable base salt thereof. 
     
     
       5. A compound as claimed in claim 2, wherein Y is NH 2 . 
     
     
       6. A compound as claimed in claim 1, wherein Z is ##STR24## in which n"is 0 or 1 and R 3  is hydrogen, methyl, ethyl, 1- or 2-propyl; R 1  is hydrogen or a pharmaceutically acceptable base salt thereof. 
     
     
       7. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-(3-amino-1- pyrrolidinyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride. 
     
     
       8. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-(ethylamino)- methyl-1-pyrrolidinyl]-4-oxo-1,4-dihydro- quinoline-3-carboxylic acid. 
     
     
       9. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-(aminomethyl)-1-pyrrolidinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. 
     
     
       10. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-(propylamino- methyl)-1-pyrrolidinyl]-4-oxo-1,4-dihydro- quinoline-3-carboxylic acid. 
     
     
       11. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-(2-propyl- aminomethyl)-1-pyrrolidinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. 
     
     
       12. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-(cyclopropylaminomethyl)-1-pyrrolidinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. 
     
     
       13. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-[[(2-hydroxyethyl)amino]methyl]-1-pyrrolidinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. 
     
     
       14. A compound as claimed in claim 1 and being 1-ethyl-5-amino-6,8-difluoro-7-[3-[[(2,2,2-trifluoroethyl)amino]methyl]-1-pyrrolidinyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. 
     
     
       15. A compound as claimed in claim 1 and being 5-amino-7-(3-amino-1-pyrrolidinyl]-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3quinolinecarboxylic acid. 
     
     
       16. A compound as claimed in claim 1 and being 5-amino-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-7-[3-[(methylamino)methyl]-1pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid. 
     
     
       17. A compound as claimed in claim 1 and being 5-amino-7-(3-amino-1-pyrrolidinyl)-8-bromo-1- cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid. 
     
     
       18. A compound as claimed in claim 1 and being 5-amino-7-(3-amino-1-pyrrolidinyl)-1-cyclo-propyl-6,8-difluoro-1,4-dihydro-4-oxo-3quinolinecarboxylic acid. 
     
     
       19. A pharmaceutical composition comprising an antibacterially effective amount of a compound as claimed in claim 1 together with a pharmaceutically acceptable carrier. 
     
     
       20. The method of treating bacterial infections in mammals which comprises administering to said mammal a pharmaceutical composition as claimed in claim 19.